marine biotechnology

1. What to do in marine biotechnology?
Johannes Tramper a,
*, Chris Battershill b
, Willem Brandenburg c
, Grant Burgess d
,
Russell Hill e
, Esther Luiten f
, Werner Mu¨ller g
, Ronald Osinga h
, Gregory Rorrer i
,
Mario Tredici j
, Maria Uriz k
, Phillip Wright l
, Rene´ Wijffels h
a
Food and Bioprocess Engineering Group, Department of Food Technology, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, Netherlands
b
Australian Institute of Marine Science, Townsville, Australia
c
Plant Research International, Wageningen, Netherlands
d
Heriot-Watt University, Edinburgh, UK
e
University of Maryland, Baltimore, MD, USA
f
Netherlands Study Center for Technology Trends, Hague, Netherlands
g
Johannes Gutenberg University, Mainz am Rhein, Germany
h
Wageningen University, Wageningen, Netherlands
i
Oregon State University, Corvallis, OR, USA
j
University of Florence, Florence, Italy
k
Center for Advanced Studies of Blanes, Blanes, Spain
l
University of Sheffield, Sheffield, UK
Abstract
During the symposium ‘‘Marine Biotechnology: Basics and Applications’’, held 25 FebruaryÁ/1 March, 2003 in Matalascan˜as,
Spain, a special brainstorm session was organized. Two questions were addressed: 1, ‘‘What is the most desirable development in
marine biotechnology’’?; 2, ‘‘What is the most spectacular development in this field in your ‘wildest’ dreams’’?The outcome of this
session is reported in this paper. From the more than 250 ideas generated, concern for the environment and human health emerged
as the most significant issues.
# 2003 Elsevier Science B.V. All rights reserved.
Keywords: Marine biotechnology; Brainstorm; Future
1. Introduction
The sea is a gigantic, largely untapped reservoir of
biodiversity. Careful and cautious exploitation is essen-
tial in order not to damage and disturb this fragile
ecosystem. The field of marine biotechnology aims to
explore and utilize this biodiversity, and has great
potential for beneficial outcomes for mankind. To
realize this aim and potential, creative thinking and
multi- and inter-disciplinary research and developments
are required. At the symposium ‘‘Marine Biotechnol-
ogy: Basics and Applications’’, held 25 FebruaryÁ/1
March, 2003 in Matalascan˜as, Spain, about 150 experts
in the field of marine biotechnology, representing all the
essential disciplines and from all over the world,
presented and discussed their work. To tap this vast
amount of gathered knowledge to its fullest extent, a
special brainstorm session was organized. The way of
brainstorming, a variant of the metaplan method, was
special in the sense that it was structured to some extent,
and that it required the active participation of preferably
all the participants of the symposium. The aim of this
session was to elicit as many new ideas as possible about
developments that sooner or later can contribute to the
sustainable exploitation of the biodiversity of the sea,
realizing that this might even be essential to meet future
requirements by mankind. After raising the ideas, they
* Corresponding author. Tel.: '/31-317-48-3204; fax: '/31-317-48-
2237.
E-mail address: hans.tramper@wur.nl (J. Tramper).
Biomolecular Engineering 20 (2003) 467Á/471
www.elsevier.com/locate/geneanabioeng
1389-0344/03/$ - see front matter # 2003 Elsevier Science B.V. All rights reserved.
doi:10.1016/S1389-0344(03)00077-7

2. were evaluated by ranking them according to the
participants preferences. This session proved that a
wealth of such ideas could be harvested in a very short
time, and that trends can be deduced easily from the
results, in particular after ranking. Besides, the pertinent
meetings were interesting and fun to participate in.
2. Procedure
There are many methods that aim to generate ideas in
an uninhibited fashion. One such method is especially
suited for groups of ideally 10Á/12 persons. In a short,
speedy meeting of maximally 1 h and 30 min, the group
is first confronted with one or two challenging ques-
tions, and 5Á/10 min are then permitted to think about
answers. Each participant then is requested to briefly
explain (2Á/3 min) and sell his or her idea. In the form of
keywords written in large letters, legible from a distance,
on post-its, the ideas are positioned and clustered on a
wall. During a short intermediate discussion, the parti-
cipants can react to each other and more ideas can be
gathered before everybody is asked to vote on his or her
favorite idea(s) by putting one or more colored stickers
on the pertinent post-it(s); each participant gets three to
five such ‘‘voting stickers’’ for each question. It is
interesting and fun to participate in such a brainstorm,
and the results can be quite spectacular, but the success
stands or falls with the way the discussion is generated
and coached. Required is a convener with some seniority
in the field, who has at least once participated in such a
session, and who is able to keep the meeting lively and
speedy.
When the idea came up to organize such a brainstorm
session during the symposium, a try-out was first done
within the marine bioprocess-engineering group of
Wageningen University. There was no doubt during
the evaluation that such a session should be incorpo-
rated in the conference. Two questions were formulated
as the most appropriate to address:
. ‘‘What is the most desirable development in marine
biotechnology’’?
. ‘‘What is the most spectacular development in this
field in your ‘wildest’ dreams’’?
Much more discussion was, however, needed before
the decision could be made on how to structure the
session. It was finally decided to have 12 identical
parallel workshops (about 150 symposium participants
were expected) all addressing the above questions, while
clustering was already pre-determined by taking the
sessions of the symposium, i.e. Phototrophic organisms,
Heterotrophic organisms and Invertebrates, as the lead
topics and further dividing these into basics and
applications, the sub-title of the symposium. Also,
division of the participants over the workshops was
not completely random; it was made sure that in each
workshop industry was represented and that national-
ities and backgrounds were heterogeneous.
A couple of weeks before the symposium, the
conveners were chosen from the registered participants
and approached with the request to undertake this task.
They all said yes, but most of them indicated that they
never had participated in such a brainstorm. For that
reason, and to make sure that the approach was similar
in all workshops, a second try-out was organized on the
second evening of the symposium with the intended
conveners as participants. That worked out well too,
and the next evening the actual workshops, with most of
the participants (about 120 of the total of 150)
contributing, were held. The day after, during the poster
session, the conveners sat together again and presented a
summary of the results of their own workshop. It
became clear that many ideas were applicable to all
three classes of organisms and, therefore, a fourth
category was added, that is General. The ideas from
all the workshops were then combined and divided
amongst these four categories. Four of the conveners
volunteered to further cluster the ideas and prepare each
a presentation of no more than 10 min for the final part
of the brainstorm: presentation of the results in a
plenary meeting with sufficient time for the participants
to comment and react to it.
3. Results
3.1. General
Looking at the results of all the workshops (Fig. 1), it
could be observed that in general most of the ideas
submitted tended to relate to environmental issues.
There were also many relevant to human health and
they were the ones that in general scored best. The idea
that a multibillion-euro successful blockbuster drug is
needed to really promote the development of marine
biotechnology was raised several times. In one of the
workshops an interesting philosophical discussion origi-
nated. It was concluded that:
. Basic and applied research cannot be easily sepa-
rated.
. ‘‘The spirit of biotechnological research is to APPLY
it’’.
Despite this, the classification ‘Basics’ and ‘Applica-
tions’ is maintained in this section as it gives the best
quantitative overview. Also, the two questions ad-
dressed are treated separately throughout the general
category. In the rest of the paper a more qualitative
description is given to prevent repetitiveness.
J. Tramper et al. / Biomolecular Engineering 20 (2003) 467Á/471468

3. 3.1.1. Most desirable developments
3.1.1.1. Basics. More than 20 ideas fell into this
category. ‘Respect for each others position in the science
economy’ got the highest score, and ‘Elucidation of the
cancer mechanism’ was the second best. Ex equo 3 and 4
were the ideas that ‘Real good projects should not have
to worry about money’ and ‘Development of genomics
and proteomics of symbionts’. A good score was also
given to ‘Sustainable use of nature for human use’.
Interesting ideas without votes are ‘Model systems for
finding bioactive compounds’, ‘Multicultural research
groups’ and ‘Independent aquaculture’.
3.1.1.2. Applications. Of the 20 ideas in this class
‘Antibacterial compounds to fight multi-resistant bac-
teria’ was the number one followed by the desire for an
‘Underwater taxonomic DNA-chip’. ‘Anti-HIV drugs’
and ‘Market-oriented approaches’ were next with the
same number of votes and ‘Sustainable development’
having one less. Ideas relating to multicultural research
groups, commercial successes and better industrial
liaison and networking did not attract votes.
3.1.2. Most spectacular developments in our ‘wildest’
dreams
3.1.2.1. Basics. Under this class only ten ideas could be
grouped with a ‘New drug selling for more than $10
billions per year’ ranking highest. ‘Clean seas’ got one
vote less, just as ‘Drugs derived from combinatorial
genetics’. Again one vote less was given to the ideas
‘Super-transformation vector’ and ‘Control of climate
by global voting’, obviously all in relation to marine
biotechnology. Ideas without votes, but nonetheless
interesting: ‘Molecular engineering basics’, ‘Fully tun-
able secondary metabolism’ and ‘Believe in basic
research’.
3.1.2.2. Applications. Not less than 31 ideas were
categorized under this class. The following table sum-
marizes them.
What are the most spectacular developments in the
field of marine biotechnology in our ‘wildest’ dreams?
Rank Score Idea
1 6 Uni-layer of antifouling cells on ship hulls
1 6 Anti-aging chemicals
1 6 Marine viagra
2 5 Peace pill
2 5 Green symbiontic fish
Á/ Food and oxygen for other planets
Á/ Marine production systems on ship
(polycultures)
Á/ Cheap, sustainable-produced food
Á/ Most of the rest (20) had similar themes to
the last three
3.2. Phototrophic organisms
About 80 ideas were classified under the category
Phototrophic organisms, which is comparable to the
number found under General. An impression of the
Fig. 1. Some of the results of the brainstorm.
J. Tramper et al. / Biomolecular Engineering 20 (2003) 467Á/471 469

4. more or less clustered ideas with the highest ranking,
provided with short comments, are given in this para-
graph or in the accompanying list.
3.2.1. Most desirable developments
In order to make algal production systems more
competitive with heterotrophic systems, in particular
more economically feasible, it is necessary either to
improve the systems or to improve the organisms so that
they are better adapted to production conditions. The
following submitted ideas reflect this desire:
. More efficient production;
. More efficient photobioreactors;
. Productivities of 60 g dry weight biomass per
illuminated square meter per day;
. Continuous systems for production of pigments,
PUFA’s, proteins, polysaccharides, etc.
. Production and harvesting are thus far two separate
domains in research. The idea ‘Integration of produc-
tion and harvesting systems’ is a plea for an
integrative, multidisciplinary approach.
With algae, it is possible to combine several functions/
applications. Reasonable efficient systems to produce
hydrogen as energy source have already been reported.
At the same time, the biomass itself can also be applied
for energy generation, CO2 sequestration or other
applications. Several ideas refer to this integrated
utilization.
Combining the latest developments in genomics,
proteomics, metabolomics and combinatorial chemistry,
it must be possible to find more efficient ways to
generate important leads in drug discovery and devel-
opment. This should be combined with efforts to scale
up production for clinical trials and obviously the final
application. Several of the generated ideas reflect these
desired developments.
Increasing the efficiency of development and produc-
tion of (functional) food is suggested.
From both agricultural practice and industrial micro-
bial applications, it can be learned that genetically
improved living organisms greatly contribute to the
final performance of the production system. Thus far,
this has received little attention in the applied algal
world. The idea ‘Genetic improvement of micro-algal
strains’ pleads for increased attention.
3.2.2. Most spectacular developments in our ‘wildest’
dreams
The rather wild idea ‘Marine viagra’ (see table above)
was actually brought in under this heading but really
points at the need for a success story, a ‘cash cow’, in the
field of marine biotechnology in general.
The rest of the submitted ideas are listed below and
accompanied by a short comment:
. The great possibilities of changing heterotrophs into
phototrophs are reflected by the idea ‘Humans with
algal chloroplasts’.
. Climate change urges for CO2 sequestration; at the
same time something useful should be done with it.
‘CO2 sequestration makes whiskey’ stands for that.
. The world has in its urban environment thousands of
hectares of unused space: roofs. Making them avail-
able for algal production, we use our space more
efficiently and lots of applications are feasible:
energy, functional food on site, etc. The idea of
‘Rooftop flat-panel photobioreactors’ aims at that.
. There is already work being done on ‘Outer-space
life-support systems’, but in view of (far) future
perspectives, this really is one of the developments
to invest in.
. This similarly holds for ‘Algae giving light’, but this
idea is also one of the possibilities to tackle scale-up
problems of photobioreactors.
. ‘Universal drug from algae’, a dream, but in view of
the potential of algal production capacity, one that
should become reality to some extent.
. ‘Hemaglobin produced in algae’ is self-explanatory in
its context.
. ‘Artificially produced diatom structures’ is in view of
the demand for diatomite, an obvious objective.
. As we have large-scale agricultural production as
opposed to horticultural production, the analogue is
to have well-controlled open-pond systems to pro-
duce algae in bulk for, e.g. food (or feed) protein. The
idea ‘Micro-algal strains optimized for open ponds’
covers this and is at the same time a plea for the
development of effective algal selection systems.
. As marine algae produce lots of complex, special
secondary metabolites, there is an obvious need for
more efforts in understanding the relevant pathways
and their biological functions. ‘Pathway understand-
ing’ is the pertinent idea.
3.3. Heterotrophic organisms
Heterotrophic marine microorganisms are future
sources of bioactive substances, industrial enzymes,
and feed for aquaculture. They are also platforms for
the biological remediation of contaminants from the
marine environment. The brainstorming process identi-
fied three major opportunities for expanding basic
research and applications of marine heterotrophic
organisms.
First, it is well known that most heterotrophic marine
organisms are not culturable in the laboratory. There-
fore, methods must be developed to isolate these
‘‘unculturable’’ marine heterotrophs from any compo-
nent of the marine environment, including deep and
shallow ocean waters, sediment, or even the surfaces of
marine organisms such as marine invertebrates or
J. Tramper et al. / Biomolecular Engineering 20 (2003) 467Á/471470

5. seaweeds. Furthermore, strategies must be developed to
rapidly obtain balanced medium formulations and
optimal cultivation conditions for the newly isolated
marine microorganisms, in other words, as one partici-
pant put it, ‘‘to tame the culturable’’.
Second, efforts to identify and produce bioactive
substances, industrial enzymes, and commodity chemi-
cals from heterotrophic marine organisms must be
stepped up. Three new tools of biotechnology*/geno-
mics, proteomics, metabolomics*/together represent a
powerful approach for discovering the next generation
of antibiotics and anti-tumor drug candidates. These
tools should also be extended to the discovery of marine
extremophiles that promote industrially significant che-
mical reactions (e.g. hydrolysis) at both high and low
temperatures over broad pH ranges. Finally, the poten-
tial of using heterotrophic organisms to produce com-
mercial fatty acids (e.g. EPA) and carotenoids (e.g.
astaxanthin) must be more thoroughly explored. Many
of these compounds are already produced by photo-
trophs, and so the possibility of turning these photo-
trophs into heterotrophs may be an exciting avenue of
research.
Third, heterotrophic marine microorganisms are un-
derutilized in aquaculture and environmental biotech-
nology. For example, heterotrophic marine organisms
may be an ideal food source for larvae of commercially
important fish and shellfish species. The economics of
commercial aquaculture processes are often limited by
low survival rates, and heterotrophic feeds may address
this issue. Finally, it is hoped that heterotrophic marine
organisms will serve as stewards for a cleaner marine
environment. For example, the use of marine micro-
organisms to clean up petroleum spills in the ocean and
coastline at the source of contamination was a dream
shared by many of the participants.
Finally, as an illustration, two ideas expressing a
‘‘dream for everyone’’:
. ‘Marine biotech companies launch three new
blockbuster products in the next 5 years based on
marine heterotroph metabolites. . .’;
. ‘Some profits go to support the marine biotech
academic research community that helped to get
them there’.
3.4. Invertebrates
Invertebrates are in general difficult organisms to
work with in many ways. This also became apparent
from the brainstorm session. It was difficult to group the
large number of ideas into a smaller number of clusters.
Invertebrates are difficult to grow, if at all, outside their
natural habitat. Invertebrate biology is still poorly
understood. The relationship with their symbionts
even less so. Genetic modification is clearly still a
dream. Most of the ideas refer to these difficulties and
can, therefore, be categorized as ‘spectacular’ or ‘wild
dream’. To mention just a few:
. Fast growing sponges (faster than men);
. Stable (transgenic) sponge cell lines;
. Expression vector system for sponges;
. Invertebrate virology under extreme conditions;
. Understanding of symbionts;
. Invertebrate (including symbionts) genomic, proteo-
mic and metabolomic technology available.
One thing is clear, if a few of the many ideas come
true, realization of the great potential of for instance
sponges, and their associated bioactive compounds of
pharmaceutical interest, will be much nearer.
4. Conclusions
As one can see, the above comprises a myriad and
wealth of ideas (foto), too many to even think of
discussing them all, even shortly. By listing them, they
at least are not lost and point in directions for research
that ultimately lead to sustainable exploitation of the
biodiversity of the sea. That is the least we can hope for,
because they represent a vast amount of knowledge: that
of all who participated! We, therefore, thank all of you
for your enthusiastic contributions. From the reports of
the conveners and from the many reactions, it can be
concluded that the brainstorm session was successful,
and interesting and fun to participate in. Finally,
‘greenness’ and ‘sustainability’ emerged as leads, as
exemplified by some really ‘wild ideas’:
. Use marine biotechnology to design ‘green biological
toys’ for entertainment purposes, for example, a
green pet or ‘living ornament’ of a marine organism
genetically designed only for aesthetic purposes.
. Green functional fish, i.e. fish genetically modified
such that it has become phototrophic and that it
produces nutraceuticals, e.g. vitamins, anti-oxidants,
etc.
. Green people genetically designed to live on Mars.
. Green mermaid, i.e. a human being genetically
modified with photosynthetic genes and genes coding
for the fish tail.
Well, let us be realistic and concentrate first on
research and developments that lead to a sustainable
exploitation of marine biodiversity!
J. Tramper et al. / Biomolecular Engineering 20 (2003) 467Á/471 471